Introduction: Hyponatremia is the most common electrolyte imbalance in hospitalized patients, associated with increased morbidity and mortality. Tolvaptan effectively raises serum sodium in SIADH. However, concerns regarding rapid overcorrection and safety persist. This study evaluates the efficacy, safety, and real-world usage patterns of tolvaptan in a tertiary care setting. Methodology: A retrospective single-centre observational study was conducted at Hospital Putrajaya using the electronic records of patients treated with tolvaptan from January 2020 to December 2025. Overcorrection was defined as >10 mmol/L increase within 24 hours, and non-response as <4 mmol/L increment at 24 hours. Results: Twenty-one patients were included, with a mean age of 66.7 years; 57% were male. Most (90.5%) received 7.5 mg initially. Mean baseline sodium was 118.1 ± 4.1 mmol/L. Tolvaptan produced rapid correction, with mean sodium increasing to 127.0 mmol/L at 24 hours (mean increment 8.9 mmol/L). Only one patient (4.8%) was a non-responder at 24 hours. Median time to sodium >130 mmol/L was 1 day, with 60% achieving this within 24 hours. At discharge, mean sodium was 130.4 mmol/L. Median length of stay following initiation was 5.5 days. Overcorrection occurred in 23.8% (n = 5), all in the 7.5 mg group, particularly among those with baseline sodium 115–120 mmol/L. No cases of osmotic demyelination syndrome (ODS) were observed. The mean internal for initiation is approximately 6 days from diagnosis. Tolvaptan usage increased and peaked in the first 3 years, but subsequently dropped and plateaued over the last 2 years. Conclusion Tolvaptan is safe and effective for sodium correction; although overcorrection remains a risk, no long-term sequelae of ODS were observed, underscoring the need for vigilant monitoring. Its use in Hospital Putrajaya remains limited, with delayed initiation possibly due to tolvaptan being considered a secondary treatment after failure of other options
Hyponatremia ; Tolvaptan

Introduction: Primary adrenal insufficiency is rare and potentially lifethreatening, with an estimated prevalence of five cases per million in Southeast Asia. Local data remain limited, and diagnosis is frequently delayed due to non-specific clinical manifestations. Widespread use of traditional medication in Malaysia may further undermine recognition, particularly when steroid exposure is concealed. We report a female on prolonged use of traditional remedies presented with classic features of Addison’s disease rather than cushingoid features, confirmed by biochemical results. Case: A 65-year-old female with underlying dyslipidemia and osteoarthritis presented with 4 days of giddiness, poor intake, nausea, and diarrhea. Further history revealed prolonged use of multiple traditional Chinese medicines, discontinued months prior, raising suspicion of prior steroid exposure. She claimed her skin has become darker over the past 2 months. She denied any infectious symptoms, contact with PTB patients, or exposure to birds. There was no family history of autoimmune disease. Clinically, she was dehydrated and hypotensive. Her blood pressure improved after fluid resuscitation. There was hyperpigmentation involving the face, extremities, tongue, and buccal mucosa. Investigation results showed severe hyponatremia (119 mmol/L), hyperkalemia (4.93 mmol/L), with normal creatinine and negative infective markers. Hyponatremia persisted despite adequate hydration. Thyroid function test was normal (Free T4 12.28 pmol/L and thyroid-stimulating hormone 4.16 µIU/mL). Morning cortisol was suppressed (37 nmol/L) with markedly elevated adrenocorticotropic hormone levels (1,134 pg/mL), confirming the diagnosis of primary adrenal insufficiency. Hence, hydrocortisone was commenced, and serum sodium was normalized 2 days later. The underlying etiology remains under evaluation, although autoimmune adrenalitis is the most likely cause. Conclusion Primary adrenal insufficiency should be considered in patients presenting with unexplained hyponatremia and hypotension. In a setting where traditional medication use is prevalent, unrecognized steroid exposure may further complicate diagnosis. A thorough clinical and appropriate biochemical assessment is crucial to differentiating primary from secondary adrenal insufficiency.
Hyponatremia

Introduction: Severe hypercalcemia is most commonly caused by primary hyperparathyroidism (PHPT) and malignancy. While standard therapies are effective in most cases, a subset of patients have persistent or refractory hypercalcemia. We present a retrospective case series detailing the clinical characteristics, biochemistry, and outcomes of patients treated with denosumab for hypercalcemia. Cases: Seven patients with severe hypercalcemia were identified, comprising five with PHPT and two with malignancyassociated hypercalcemia. The mean age was 70.4 years (range 55–86), with 71% female (n = 5) and 29% male (n = 2). Baseline corrected calcium ranged from 2.92 to 4.59 mmol/L, with a mean of 3.26 mmol/L. In the PHPT cohort, parathyroid hormone (PTH) levels were significantly elevated (16.7–168 pmol/L), while malignancy patients had suppressed PTH (0.6 and 0.9 pmol/L). Prior to denosumab, 4/7 patients (57%) received bisphosphonates, 3/7 (43%) received calcitonin, and 1/7 (14%) was treated with cinacalcet. Denosumab resulted in a mean reduction in corrected calcium of 0.22 mmol/L from 3.26 to 3.03 mmol/L. Biochemical response was observed in 5/7 patients (71%). Of these, 3 patients (43%) achieved normocalcemia, while 2 patients (29%) demonstrated a partial response. The remaining 2/7 patients (29%) showed no significant improvement in calcium levels. Among responders, the mean time to calcium reduction to <3.0 mmol/L was 27 days (range 7–47). Repeat dosing was required in the majority of patients, with a mean of 1.7 doses per patient (range 1–4), indicating variability in both onset and durability of response. Among patients with PHPT, four underwent parathyroidectomy, and one declined surgery. Both patients with malignancy were managed nonsurgically. Conclusion Denosumab achieved normocalcemia in 43% of patients, with additional partial responses. Its effects were variable, with delayed response and frequent need for repeat dosing, supporting its role as an adjunctive or bridging therapy rather than as a definitive treatment.
Denosumab ; Hypercalcemia ; Retrospective Studies

Introduction: Hypocalcemia in patients with advanced malignancy is usually attributed to bone metastases, vitamin D deficiency, renal impairment, or antiresorptive therapy. Paclitaxel, a taxane-based chemotherapy agent widely used for breast cancer, is not commonly associated with calcium disturbances. Proposed mechanism includes renal tubular dysfunction, renal salt wasting, and disruptions in bone metabolism. In patients with underlying disorders of calcium homeostasis such as hypoparathyroidism, taxanebased chemotherapy such as Docetaxel and Paclitaxel may exacerbate calcium imbalance. We reported a case of recurrent hypocalcemia associated with paclitaxel therapy in a patient with metastatic breast cancer. Case: A 42-year-old female with metastatic breast cancer, involving the liver and bones, had previously undergone neoadjuvant chemotherapy, mastectomy, and adjuvant radiotherapy. Following the disease progression, she was commenced on weekly intravenous paclitaxel at a 20% dose reduction due to prior complications and underlying metabolic risk. She had a history of post-thyroidectomy hypoparathyroidism and had previously been intolerant to docetaxel during the neoadjuvant chemotherapy, which was complicated by hypocalcemia, likely secondary to renal salt wasting. During paclitaxel treatment, she developed recurrent symptomatic hypocalcemia, requiring multiple hospital admissions and repeated intravenous calcium gluconate infusions despite ongoing oral calcium and calcitriol supplementation, which were temporarily increased during the chemotherapy. These episodes occurred intermittently in temporal association with paclitaxel administration, with other causes of hypocalcemia were considered less likely. Conclusion Hypocalcemia associated with paclitaxel is rarely described in literature. This case highlights the importance of monitoring calcium level in patients receiving paclitaxel, particularly in those with pre-existing hypoparathyroidism.
Hypocalcemia ; Hypoparathyroidism ; Breast Diseases ; Paclitaxel

Introduction: Severe hypercalcemia is a life-threatening metabolic emergency that necessitates prompt initiation of systemic therapy due to the risk of cardiac arrhythmias. It is frequently linked to squamous cell carcinoma through the production of parathyroid hormone–related protein, which mediates the development of humoral hypercalcemia of malignancy. Case: This is a case of a 38-year-old male who was diagnosed 1 year ago with locally advanced poorly differentiated basaloid squamous cell carcinoma of the lower anterior mandibular alveolus involving cortical, medullary bone, and perineural invasion. He underwent extensive tumor resection with reconstruction, tracheostomy, and bilateral neck dissection, followed by multiple revision surgeries for postoperative complications. He completed adjuvant chemoradiotherapy. He presented with acute confusion without other systemic symptoms. His Glasgow Coma Scale was E4V4M5. Neurological and systemic examinations were unremarkable, and oral cavity assessment showed no evidence of recurrence. Investigations revealed severe hypercalcemia (5.94 mmol/L) with normal phosphate (1.16 mmol/L) associated with shortened QTc. Other tests were unremarkable, with no evidence of infection, uremia, liver dysfunction, or alternative metabolic causes. Lumbar puncture was unremarkable. His parathyroid hormone level was suppressed at 0.50 pg/ mL. Computed tomography brain showed no evidence of meningoencephalitis, hydrocephalus, cerebral oedema, or metastasis. Aggressive hydration was initiated alongside subcutaneous calcitonin, which was subsequently titrated. However, there was no clinical or biochemical improvement after 1 day, with persistent confusion and calcium remaining at 5.87 mmol/L. Subcutaneous denosumab was then administered, and hemodialysis was initiated on alternate days due to refractory hypercalcemia. This resulted in improvement of calcium levels to 3.2–3.6 mmol/L and resolution of confusion Conclusion Refractory hypercalcemia may represent a late manifestation of advanced squamous cell carcinoma and is an ominous prognostic indicator, necessitating prompt evaluation and oncologic management.
Calcitonin ; Denosumab ; Hypercalcemia ; Renal Dialysis ; Neoplasms

Introduction: Atypical parathyroid adenoma (APA) constitutes approximately 0.5–4.0% of all cases of primary hyperparathyroidism (pHPT). Here, we report a case of APA presenting with severe hypercalcemia, complicated with renal impairment, bilateral medullary nephrocalcinosis, and multiple fragility fractures. Case: A 45-year-old male initially presented with a 6-month history of constipation, polyuria, lethargy, bone pain, and difficulty in initiating micturition. Laboratory investigations revealed impaired renal function with an estimated glomerular filtration rate of 41.4 mL/min, severe hypercalcemia (4.07 mmol/L), and an elevated intact parathyroid hormone (iPTH) level of 104.0 pmol/L (reference range: 1.58–6.03 pmol/L), confirming the diagnosis of pHPT. He was also found to have vitamin D deficiency, with a serum total 25-hydroxyvitamin D level of 46 nmol/L. Ultrasound of the abdomen demonstrated bilateral medullary nephrocalcinosis, while neck ultrasound and Tc-99 m sestamibi parathyroid scintigraphy revealed a concordant lesion in the posterior aspect of the left thyroid lobe, suggestive of a parathyroid adenoma. He returned 3 months later with closed fractures of the right subtrochanteric femur and the right humerus following a fall from standing height. In view of persistent hypercalcemia despite hyperhydration and treatment with zoledronic acid, subcutaneous denosumab (60 mg) was administered, resulting in an improvement in serum calcium levels. A left inferior parathyroidectomy was then performed concurrently with internal fixation of the right femur. The surgery was uneventful. Histopathological examination confirmed an atypical parathyroid adenoma. Postoperatively, the serum calcium and iPTH levels normalized, and the patient remained asymptomatic and normocalcemic during regular follow-up. Conclusion APA remains a diagnostic and therapeutic challenge due to its clinical, biochemical, and histopathological features of equivocal malignancy. Surgical resection remains the mainstay of management of APA, and long-term surveillance is essential in view of its uncertain malignant potential and risk of recurrence.
Hypercalcemia ; Parathyroid Neoplasms

Introduction: Electrolyte imbalance is common in central nervous system infections. Arginine vasopressin deficiency (AVP-D), Cerebral Salt Wasting (CSW), and Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) are important etiologies that can cause opposing extremes of serum sodium, posing diagnostic and therapeutic challenges. We report a rare case of transient central AVP-D followed by CSW secondary to tuberculous meningitis (TBM). Case: An 18-year-old female presented with a 1-month history of fever, reduced responsiveness, and visual hallucinations. Her Glasgow Coma Scale was E4V1M4 with neck stiffness and upper motor neuron signs. Initial investigations revealed severe hyponatremia (119 mmol/L) and communicating hydrocephalus with third ventricle ballooning on brain imaging. Coupled with a positive tuberculosis contact, anti-tuberculous therapy was initiated for probable TBM alongside 3% saline correction prior to insertion of external ventricular drain (EVD). Her condition deteriorated on day 5, requiring intubation for aspiration pneumonia. Repeated imaging showed worsening hydrocephalus, necessitating EVD revision. She subsequently developed polyuria (urine output [UO] 150–300 mLs/hour), with biochemical findings consistent with AVP-D (serum sodium 154 mmol/L; urine osmolality 96 mOsm/kg; urine sodium <20 mmol/L). Intravenous desmopressin 1 mcg was administered, and UO reduced to 30 mLs/hour. However, polyuria recurred on Day 9, accompanied by tachycardia, hypotension, and a rapid decline in serum sodium to 120 mmol/L. Diagnosis of CSW was established (urine sodium 204 mmol/L; urine osmolality 470 mOsm/kg). Oral fludrocortisone was initiated and titrated to 0.4 mg daily to maintain serum sodium >130 mmol/L. Due to persistent hydrocephalus, right ventriculoperitoneal shunt was inserted on Day 22, after which her UO gradually decreased, allowing tapering of fludrocortisone. She remains on fludrocortisone 0.1 mg daily with ongoing rehabilitation. Conclusion TBM can be complicated by SIADH, AVP-D, or CSW. Concurrent AVP-D and CSW have not been reported. This case highlights the dynamic electrolyte disturbances in TBM which may lead to diagnostic confusion and therapeutic error. Early recognition and tailored therapy, alongside definitive management to reduce intracranial pressure, are essential for optimal outcomes.
Hypernatremia ; Hyponatremia ; Tuberculosis, Meningeal

Introduction: Hypernatremia is a common yet high-mortality electrolyte disorder. The hypothalamus maintains water homeostasis via thirst sensation and arginine vasopressin (AVP) secretion. Hypothalamic tumors, such as gliomas, can progressively destroy these osmoregulatory centres, leading to “malignant” hypernatremia (>180 mmol/L). We report a case of life-threatening hypernatremia in a patient with a progressive hypothalamic glioma, exploring its complex pathophysiology. Case: A 41-year-old female with a progressive high-grade hypothalamic glioma and persistent hydrocephalus presented with generalized weakness, reduced oral intake, and dehydration. Her initial Glasgow Coma Scale was E4V3M6. Laboratory investigations revealed malignant hypernatremia (serum sodium 209 mmol/L) and a serum osmolarity of 441 mOsm/kg. Despite life-threatening dehydration (urea 26.2 mmol/L, creatinine 343 umol/L), she was still able to deceptively produce urine output of 400 mL/day with a concentrated urine osmolarity of 890 mOsm/kg. A 1 mcg IV desmopressin trial reduced urine output to 60 mL/day and serum sodium by 10 mmol/L within 14 hours, confirming relative AVP deficiency. The patient’s malignant hypernatremia was gradually corrected to 168 mmol/L over 1 week (8–12 mmol/L/day) using controlled intravenous hydration. However, her condition deteriorated due to hospital-acquired infection, and she succumbed 10 days after admission. Conclusion This case underscores several critical learning points for managing hypothalamic emergencies. First, hypothalamic tumors can reset the osmostat or destroy osmoregulatory centres, causing adipsic AVP deficiency. Second, clinicians must be alert to “masked polyuria” where severe hypovolemia reduces the glomerular filtration rate, causing urine output to appear “normal” despite underlying AVP deficiency. This state of “relative polyuria” is a hallmark of hypothalamic hypernatremia, thus indicating that a normal urine output does not rule out AVP deficiency. While desmopressin is indicated, its use in adipsic patients demands strict fluid titration to prevent iatrogenic hyponatremia. Rapid hypotonic correction carries a proven risk of cerebral oedema, and sodium measurement accuracy varies significantly across laboratory methods in extreme ranges.
Hypernatremia ; Hypothalamic Neoplasms

Introduction: ABCD syndrome (ABnormal Calcium-CreatinineCalcinosis in Down syndrome) is a rare tetrad of hypercalcemia, hypercalciuria, nephrocalcinosis, and renal impairment in children with Down syndrome, often with delayed diagnosis resulting in irreversible renal damage. : We report a 7-year-old male with Down syndrome, who previously had a stormy neonatal period due to large atrialseptal-defect and pulmonary hypertension, and required surgery at 3-years-old with prior prolonged ventilation. He was since bedbound with severe spastic diplegia, complicated by GERD and food aversion, requiring nasogastric tube feeding. He was discovered to have hypercalcemia and renal impairment during admission in district hospital for febrile illness with gastrointestinal symptoms. Initial serum calcium was 2.78 mmol/L, phosphate 1.54 mmol/L, magnesium 0.96 mmol/L, ALP 210 IU/L, urea 18.6 mmol/L, and creatinine 266 umol/L. Renal impairment did not improve and ultrasound KUB revealed bilateral small kidneys with medullary nephrocalcinosis. Consultation with the paediatric nephrologist concluded as CKDstage-4. He was transferred to our centre. He demonstrated severe hypercalcemia (3.44 mmol/L), hypercalciuria (urinecalcium-to-creatinine-ratio of 1.17 mmol/mmol, >95 th%), and suppressed iPTH (0.9 pmol/L,1.6–6.9), suggesting PTH-independent process. 25-OH-Vit-D3 was 134 nmol/L (74–250, sufficient). He was more irritable and moody, but no seizures. ECG was normal. Skeletal assessment did not reveal osteolytic changes or increased resorption. He was investigated by paediatric hemato-oncologists, with negative findings, despite extensive search for hematological or bone malignancy and granulomatous disease. His ESR and immunoglobulin level was high for unknown reasons. He was treated with intravenous and oral hydration, dietary calcium restriction with modified lowcalcium formula, assisted by dietitian, and IV pamidronate infusion (0.125 mg/kg) stat dose, resulting in stabilization of serum calcium level (2.5 mmol/L), which persisted for about 8 weeks during follow-up. Conclusion ABCD syndrome should be considered in Down syndrome children presenting with unexplained hypercalcemia. Early recognition and intervention are vital.
ABCD syndrome ; Down Syndrome ; Hypercalcemia

Introduction: Hypernatremia in preterm babies is often due to insensible water loss, inadequate fluid intake or sodium imbalance due to immature kidneys. Congenital nephrogenic diabetes insipidus (CNDI) is an uncommon cause of hypernatremia in neonates and presents shortly after birth. Early recognition is important to prevent severe dehydration, electrolytes imbalance and neurological complications. Case: We report a case of a preterm 32-week female infant, with a birth weight of 1.14 kg with persistent hypernatremia (146– 156 mmol/L) from day 4 of life. She received total parenteral nutrition since birth and was started on breastmilk since day 5 of life. The baby was mildly dehydrated with weight loss and high urea (6.5 mmol/L) at day 7 of life. Total fluids were increased to 160 mL/kg/day but serum sodium remained elevated even though the urea had normalized. The infant was also noted to have high urine output (5–6 mL/kg/hour) since day 3 of life and suboptimal weight gain. Further evaluation at age 1 month revealed urine osmolality 71 mOsm/kg, serum osmolality 308 mOsm/kg and urine sodium <20 mmol/L when serum sodium was 150 mmol/L, suggestive of DI. A trial of desmopressin showed unchanged serum sodium (Na), suggesting nephrogenic DI. Administration of intravenous fluids of 1/5NSD10% resulted in further increase of both sodium (159 mmol/L) and serum osmolality (326 mOsm/kg) with low urine osmolality (111 mOsm/kg). Intravenous fluids were discontinued and she was started on hydrochlorothiazide (1 mg/kg/dose bd), resulting in gradual normalization of sodium 138 mmol/L. Post discharge, she had good weight gain and normal developmental milestones at corrected age of 1.5-month-old. Due to early onset hypernatremia, the infant was referred for genetic testing to rule out CNDI. Conclusion Early onset persistent hypernatremia and high urine output despite adequate fluid management should prompt evaluation of DI. Early diagnosis is crucial to prevent a chronic state of hypernatremia that can lead to growth and developmental delay.
Infant, Newborn ; Dehydration ; Hypernatremia